Chronic Obstructive Pulmonary Disease:

Transcription

1 Chronic Obstructive Pulmonary Disease: THE BASICS PROF.G.E. ERHABOR Consultant Chest Physician Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria. 1

2 BASICS IS THE ESSENCE OF GREATNESS, THE MOTHER OF ALL KNOWLEDGE. Dr. G. E. Erhabor B U R D E N O F C O P D COPD is the 4th leading cause of death in the USA (behind heart disease, cancer, and cerebrovascular disease). In 2000, the WHO estimated 274 million deaths worldwide from COPD In 1990, COPD was ranked 12th as a burden of disease by 2020 it is projected to rank 5th. Prevalence and morbidity data greatly underestimate the total burden of COPD because the disease is usually not diagnosed until it is clinically apparent and moderately advanced. The WHO estimate 1.1 billion smokers worldwide, increasing to 1.6 billion in In low and middle income countries rates are increasing at an alarming rate. COPD is the only chronic disease that is showing progressive upward trend in both mortality and morbidity. Cigarette smoking is the primary cause of COPD although in low income countries, indoor pollution may be a primary causative factor. In Algeria, the prevalence of tuberculosis and acute respiratory infections has decreased since 1965; an increase in COPD and asthma has been observed in the last decade. COPD is a more costly disease than asthma, and depending on country, 50-75% of the costs are for services associated with exacerbation. Despite this burden, COPD is a Cinderella condition that receives limited recognition from both patients and physicians Respiratory Medicine 2002; 96: S1-S31 2

3 Disease Trajectory of a Patients with COPD Chronic bronchitis Chronic bronchitis is defined clinically as the presence of a cough productive of sputum not attributable to other causes on most days for at least three months over two consecutive years 3

4 Emphysema Emphysema is defined anatomically as a permanent and destructive enlargement of airspaces distal to the terminal bronchioles without obvious fibrosis and with loss of normal architecture 4

5 DEFINITION OF COPD Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease state characterized by a airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produce significant systemic consequences. The current GOLD and ATS/ERS definition for airflow limitation is an FEV1/FVC ratio of < 70% ( FEV1 predicted < 80%) COPD TWO HISTORICAL HYPOTHESIS DUTCH HYPOTHESIS- A group from Groningen led by Professor Orie introduced the term Chronic non-specific Lung in This approach called Dutch hypothesis which states that airway obstruction like Asthma, chronic bronchitis, COPD and emphysema is related to a different expression of primary abnormality in the airways. BRITISH HYPOTHESIS- Propose that smoking causes mucous hypersecretion and impaired host defenses leading to Chronic infections, disseminated bronchiolar obstruction and emphysema. 5

6 Diagrammatic representation of the four main conditions that comprises COPD The decline in lung function as part of the normal ageing process and as accelerated by cigarette smoking 6

7 Loss of lung function over 11 years in the Lung Health Study for continuous smokers ( ) intermittent quitters ( ) and sustained quitters ( ). FEV1:L forced expiratory volume in one second. Figured reproduced with permission from [18]. INFLAMMATION Small airway disease Airway inflammation Airway remodeling Parenchymal destruction Loss of alveolar attachments Decrease of elastic recoil AIRFLOW LIMITATION 7

8 ASTHMA Sensitizing agent COPD Noxious agent Asthmatic airway inflammation CD4+ T-lymphocytes Eosinophils COPD airway inflammation CD8+ T-lymphocytes Macrophages Neutrophils Completely reversible Airflow limitation Completely irreversible Pathogenesis of COPD Noxious particles and gases Anti-oxidants Lung inflammation Host factors Anti-proteinases Oxidative stress Proteinases 8 COPD pathology Repair mechanisms

9 Causes of Airflow Limitation Irreversible Fibrosis and narrowing of the airways Loss of elastic recoil due to alveolar destruction Destruction of alveolar support that maintains patency of small airways Causes of Airflow Limitation Reversible Accumulation of inflammatory cells, mucus, and plasma exudates in bronchi Smooth muscle contraction in peripheral and central airways Dynamic hyperinflation during exercise Cells and Mediators Involved in the Pathogenesis of COPD RISK FACTORS FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE Host factors Genetic factors Sex Exposures Smoking Socio-economic state 9

10 Airway hyper reactivity 1gE and asthma Occupation Environmental pollution Perinatal events and childhood illness. Infections Recurrent Bronchopulmonary Aspergillosis Diet Assess and Monitor Disease: Key Points Indoor pollution e.g. Cooking indoors Diagnosis of COPD is based on a history of exposure to risk factors and the presence of airflow limitation that is not fully reversible, with or without the presence of symptoms. Patients who have chronic cough and sputum production with a history of exposure to risk factors should be tested for airflow limitation, even if they do not have dyspnea. For the diagnosis and assessment of COPD, spirometry is the gold standard. Health care workers involved in the diagnosis and management of COPD patients should have access to spirometry. DIAGNOSIS OF COPD 10

11 Consideration in Performing Spirometry 1 Preparation Spirometers need calibration on a regular basis. Spirometers should produce hard copy to permit detection of technical errors. The supervisor of the test needs training in its effective performance. Maximal patient effort in performing the test is required to avoid errors in diagnosis and management Performance Spirometry should be performed using techniques that meet published standards. The expiratory volume/time traces should be smooth and free from irregularities. The recording should go on long enough for a volume plateau to be reached, which may take more than 12 seconds in severe disease. Both FVC and FEV1 should be the largest value obtained from any of 3 technically satisfactory curves and the FVC and FEV1 values in these three curves should vary by no more than 5% or 100 ml, whichever is greater 11

12 Evaluation Spirometry measurements are evaluated by comparison of the results with appropriate reference values based on age, height, sex, and race The presence of a postbronchodilator FEV1 < 80% predicted together with an FEV1/FVC < 70% confirms the presence of airflow limitation that is not fully reversible. In patients with FEV1 80% predicted, FEV1/FVC < 70% may be an early indicator of developing airflow limitation. Bronchodilator Reversibility Testing 1 Preparation Test should be performed when patients are clinically stable and free from respiratory infection. Patients should not have taken inhaled short-acting bronchodilators in the previous six hours, long-acting β2 agonists in the previous 12 hours, or sustained release theophyllines in the previous 24 hours. Spirometry FEV1 should be measured before a bronchodilator is given. The bronchodilator should be given by metered dose inhaler through a spacer device or by nebulizer to be certain it has been inhaled. The bronchodilator dose should be selected to be high on the dose/response curve. Suitable dosage protocols are 400 µg β2-agonist, 80 µg anticholinergic, or the two comined. FEV1 should be measured again minutes after the bronchodilator is given. Results 12

13 An increase in FEV1 that is both greater than 200 ml and 12% above the prebronchodilator FEV1 is considered significant. 13

14 Impaired Lung Function is an excellent predictor of: 1. Morbidity 2. Mortality 3. The development of lung cancer 4. Functional impairment 5. Elevated C-reactive protein 6. Osteoporosis 7. Death 14

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17 Objectives of COPD Management Prevent disease progression Relieve symptoms Improve exercise tolerance Improve health status Prevent and treat exacerbations Prevent and treat complications Reduce mortality Minimize side effects from treatment MANAGEMENT Goals of the therapy: 1. Education 2. Retard the process of airflow limitation 3. Minimizing airflow limitation 4. Eliminate and prevent infection 17

18 5. Correction of complications like hypoxaemia and Cor pulmonale 6. Rehabilitation physical, occupational, psychological. 7. Surgery Spirometric Classification of Chronic obstructive pulmonary disease (COPD) Severity Postbronchodilator FEV 1 %pred FEV 1 /FVC At risk # > Mild COPD Moderate COPD Severe COPD Very severe 0.7 <30 FEV1: forced expiratory volume in one; FVC: forced vital capacity. #: patients who smoke or have exposure to pollutants, have cough, sputum or dyspnea BTS AND GOLD CLASSIFICATIONS OF SEVERITY OF COPD BTS Classification GOLD Classification Mild disease FEV %predicted FEV1>80% predicted but FEV1/FVC >70% (stage1) Moderate disease FEV %predicted FEV % predicted (stage IIA) predicted + respiratory or Right heart failure (stage IIB) Severe disease FEV1<40% predicted FEV1<30%predicted or FEV1<50% predicted + 18

19 respiratory or right heart failure. Management of COPD Stage 0: At Risk Characteristic Recommended treatment Management of COPD Stage I: Mild COPD Characteristics Recommended Treatment 19

20 Management of COPD Stage II: Moderate COPD Characteristics Recommended Treatment Management of COPD Stage IV: Very Severe COPD Characteristics Recommended Treatment 20

21 OXYGEN THERAPY Cumulative percent survival of patients in the Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) controlled trials of long-term domiciliary therapy for men aged over 70. The control subject (. -.) received no oxygen; the NOTT subject (...) received oxygen for 12 hours in the 24-hour day, including the sleeping hours; MRC O 2 subjects ( ) received oxygen for 15 hours in the 24 hour day, including the sleeping hours; and continuous oxygen therapy (COT) subjects (- - -) received oxygen for 24 hours in the 24 hour day (on average, 19 hours). (From Flenley DC: Long-term oxygen therapy. Chest 87:99-193, 1985). MANAGEMENT OF COPD ADVANTAGES / ADMINISTRATION OF VARIOUS FORMS OF THERAPEUTIC INTERVENTION ADVANTAGES ADMINISTRATION Smoking morbidity and mortality 1. Ask Cessation Improved pulmonary function 2. Advice 21

22 Improved subjective symptom 3. Assess - willingness to quit More drastic in mild COPD 4. Assist quit plan Counseling Social support Pharmacotherapy Anti depressant bupropion 5. Arrange: Follow-up contact Bronchodilators 1.Smooth muscle relaxation SA (Short acting βagonist) + anti cholinergic 2. Improved lung emptying Combined LA-BD/SA-BD during tidal breathing 3. Increase (small in FEV1) LA-BD + ICS + theophyline 4. Large changes in lung Vol. Tiotropium is more effective than Ipratropium bromide. 5. Reduced residual volume 6. Delay asset of dynamic hyperinflation 7. Reduced perceived Breathlessness Anti cholinergic may also have Some anti inflammatory properties 22

23 ADVANTAGES ADMINISTRATION ADVANTAGES ADMINISTRATION 23

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25 ADVANTAGES ADMINISTRATION 25

26 ADVANTAGES ADMINISTRATION LONG-TERM EFFECT OF INHALED STEROID STUDY MULTICENTRE STUDY NO. OF PATIENTS ENROLLED RATE OF FEV 1 DECLINED PLACEBO HEALTH OUTCOMES Euroscope NEJM June people recruited, 1277 participated, mean age 52 years (Fluticasone 800µg/day placebo) Small difference between two groups overall 3 years decline in FEV 1 140ml in the budesonide group and 180ml in placebo Not evaluated Initial improvement for 6/12 followed by a similar decline 9-36mts. 26

27 Isolide Lancet May pts mild moderate fluticasone 500µg twice daily with placebo in moderate/severe COPD 3years period) FEV 1 decline 133L in fluticasone group FEV litres in placebo improvement marked 6-9mts later revert to similar levels. Exacerbation low in fluticasone group. Steroid group had slower rate of decline of health status. STUDY MULTICENTRE STUDY NO. OF PATIENTS ENROLLED RATE OF FEV 1 DECLINED PLACEBO HEALTH OUTCOMES Copenhagen Lung study Lancet May 1999 Vestibo et al, budesonide 800µg per day/placebo. Mild improvement of lung function Decline in FEV 1 was identical 46ml per year for budesonide 48ml placebo. No Charge Isolide Lancet May patients with mild COPD FEV 1 68 percent predicted) and treated with inhaled steroid tramcinolone placebo for (3years) No effect in decline of FEV 1. Symptoms Bone density in steroid group Increased skin bruising Reduced hospitalization 27

28 Effect of commonly used medications on important clinical outcomes in chronic obstructive pulmonary disease FEV1 Lung volume Dyspne a HRQo L AE Exercise enduran ce Disease modifie r by FEV1 Mort ality Side effect Shortacting β - agonist Yes (A) Yes (B) Yes (A) NA NA Yes (B) NA NA Some Ipratropium bromide Yes (A) Yes (B) Yes (A) NO (B) Yes (B) Yes (B) NO NA Some Long-acting β -agonist Yes (A) Yes (A) Yes (A) Yes (A) Yes (A) Yes (B) (NO) NA Minimal Tiotropium Yes (A) Yes (A) Yes (A) Yes (A) Yes (A) Yes (B) NA NA Minimal Inhaled corticostero ids Yes (A) NA Yes (B) Yes (A) Yes (A) NA NO NA Some Theophylin e Yes (A) Yes (B) Yes (A) Yes (B) NA Yes (B) NA NA Important FEV1 : forced expiratory volume in one second; health related quality of life; AE: exacerbation of COPD; NA: evidence not available Gold grade levels are indicated in bracts. 28

29 Therapy at Each Stage of COPD Patients must be taught how and when to use tier treatment and treatments being prescribed for other conditions should be reviewed. Beta-blocking agents (including eye drop formulations) should be avoided. All Stages Avoid risk factors Education Influenza vaccine once or twice yearly Stage 0: At Risk Spirometry normal Chronic symptoms (cough, sputum production) Stage I: Mild COPD FEV1/FVC < 70% FEV1? 80% predicted Short-acting bronchodilator as needed With or without chronic symptoms (cough, sputum production) Stage II: Moderate COPD FEV1/FVC < 70% 30%? FEV1 < 80% predicted With or without chronic symptoms (cough, sputum production, dyspnea) If symptomatic Regular bronchodilator treatment plus short-acting bronchodilator as needed 29

30 Consider inhaled glucocorticosteroids Rehabilitation Stage III: Severe COPD FEV1/FVC < 70% FEV1 < 30% predicted OR Fev1 < 50% predicted plus respiratory failure or clinical signs of right heart failure Regular bronchodilator treatment plus short-acting bronchodilator as needed Consider inhaled glucocorticosteroids Rehabilitation Long-term oxygen therapy if respiratory failure is present Consider surgical treatments INDICATION FOR LONG-TERM DOMICILLARY OXYGEN THERAPY (LTOT) 1. Patients Should Not Smoke. 2. PaO2 / 7.5kpa (56mmHg) when clinically stable (i.e. at 4-5 weeks after exacerbation. 30

31 3. PaO2 / 5.0kpa (38mmHg) when clinically stable (i.e. at least 4-5 weeks after exacerbations. 4. Previous Cor-pulmonale (ankle Oedema/raised jugular venous pressure abnormal blood gases) 5. Forced expiratory volume in 1 sec/1.5 litres and forced vital capacity of 72 litres. PROGNOSTIC SURVIVAL / FACTORS Aged under 60 and FEV1 above 50% predicted 90% 3-year survival Aged over 60 and FEV1 above 50% predicted 80% 3-year survival Aged over 60 and FEV % predicted 75% 3-year survival 3 Levels of Management of Acute Exacerbations Level I - Outpatient Treatment Level II - Treatment for Hospitalized patients 31

32 Level III - Treatment in patients requiring special or intensive care unit Clinical history, physical findings and diagnostic procedures in patients with exacerbation of chronic obstructive pulmonary disease (COPD) Clinical history Level 1 Level II Level III Co-morbid conditions# History of frequent exacerbation Severity of COPD Mild /moderate Moderate /severe Severe Physical findings Haemodynamic Stable Stable Stable evaluation /unstable Use accessory respiratory Not present muscles, tachypnoea Persistent symptoms after No initial therapy Level 1 Level I Level III Diagnostic procedures Oxygen saturation Yes Yes Yes Arterial blood gases No Yes Yes Chest radiograph No Yes Yes Blood tests No Yes Yes 32

33 Serum drug if applicable if application If applicable concentration + Sputum gram stain and No Yes Yes culture Electrocardiogram No Yes Yes +: unlikely to be present; ++: likely to be present; +++: very likely to be present. #: the more common co-morbid conditions associated with poor prognosis in exacerbations are congestive heart failure, coronary artery disease, diabetes mellitus, renal and liver failure; blood tests include cell blood count, serum electrolytes, renal and liver function; +: serum drug concentration, consider if patients are using theophylline, warfarin, carbamezepine, digoxin; consider if patient has recently been on antibiotics Indications for Hospital Assessment or Admission for Acute Exacerbations of COPD* Marked increase in intensity of symptoms, such as sudden development of resting dyspnoea Severe background COPD Onset of new physical signs (e.g. Cyanosis, peripheral edema) Failure of exacerbation to respond to initial medical management Significant co morbidities Newly occurring arrhythmias Diagnostic uncertainty Older age Insufficient home support Indications for ICU Admission of Patients with Acute Exacerbations of COPD Severe dyspnea that respond inadequately to initial emergency therapy 33

34 Confusion, lethargy, coma Persistent or worsening hypoxemia (pao2 < 6.7 kpa, 50 mm hg) despite supplemental oxygen, and/or severe/worsening hypercapnia (paco2 > 9.3 kpa, 70 mm hg) and/or severe/worsening respiratory acidosis (ph < 7.30) Management of Severe but Not Life-threatening Exacerbations of COPD in the Emergency Department or the Respiratory Ward* Assess severity of symptoms, blood gases, chest X-ray Administer controlled oxygen therapy repeat arterial blood gas measurement after 30 minutes Bronchodilators: - Increase dose or frequency - Combine β2-agonists and anticholinergics - Use spacers or air-driven nebulizers - Consider adding intravenous aminophylline, if needed Glucocorticosteroids Oral or intravenous Antibiotics - When signs of bacterial infection, oral or occasionally intravenous Consider mechanical ventilation At all times - Monitor fluid balance and nutrition - Consider subcutaneous heparin - Identify and treat associated condition (e.g. heart failure, arrhythmias) - Closely monitor condition of the patient 34

35 *The management of acute exacerbations of COPD in the hospital depends on the facilities of the local hospital. Indications for Invasive Mechanical Ventilation Indications for Invasive Mechanical Ventilation Severe dyspnea with use of accessory muscles and paradoxical abdominal motion. Respiratory Frequency > 35 breaths per minute Life-threatening hypoxemia (PaO 2 < 5.3 kpa, 40 mm Hg or PaO 2 /FiO 2 < 200) Severe acidosis (ph < 7.25) and hypercapnia (PaCO 2 > 8.0 kpa, 60 mm Hg) Respiratory arrest Somnolence, impaired mental status Cardiovascular complications (hypertension, shock, heart failure) Other complications (metabolic abnormalities, sepsis, pneumonia, pulmonary embolism, barotrauma massive pleural effusion)nippv failure (or exclusion criteria,) NIPPV failure (or exclusion criteria,) 35

36 Selection and Exclusion Criteria for NIPPV Discharge Criteria for Patients with Acute Exacerbations of COPD Inhaled β2-agonist therapy is required no more frequently than every 4 hours Patient, if previously ambulatory, is able to walk across room Patient is able to eat and sleep without frequent awakening by dyspnoea Patient has been clinically stable for hours Arterial blood gases have been stable for hours Patients (or home caregiver) fully understands correct use of medications Follow-up and home care arrangements have been completed (e.g. visiting nurse, oxygen delivery, meal provisions) Patient, family, and physician are confident patient can manage successfully 36

37 Follow-up Assessment 4-6 Weeks After Discharge from Hospital for an Acute Exacerbation of COPD Ability to cope in usual environment Measurement of FEV1 Reassessment of inhaler technique Understanding of recommended treatment regimen COPD) Need for long-term oxygen therapy and/or home nebulizer (for patients with severe Opportunities for Preventing COPD Primary: Preventing development of disease Smoking abstinence Smoking cessation Minimize indoor pollution Secondary: Early detection and prevention of symptomatic disease Smoking cessation Spirometric measurement of expiratory flow rate and nonspirometric measurement of force expiratory time in high-risk persons (smokers) α1-antitrypsin replacement therapy for person at risk for emphysema because of a genetic deficiency syndrome* Tertiary: Reducing complications in symptomatic disease Smoking cessation Influenza and pneumococcal vaccination Pulmonary rehabilitation Supplemental oxygen for patients with hypoxemia * α1-antitrypsin replacement therapy is indicated only for persons with proven α1-antitrypsin deficiency and evidence of abnormal lung function. Such replacement therapy, however, has not yet been proved to prevent the progression of disease. 37

38 Addendum: Brief Strategies to Help the Patient Willing to Quit Smoking 1. ASK: Systematically identify all tobacco users at every visit. Implement an office-wide system that ensures that, for EVERY patient at EVERY clinic visit, tobacco-use status is queried and documented 2. ADVISE: Strongly urge all tobacco users to quit. In a clear, strong, and personalized manner, urge every tobacco user to quit. 3. ASSESS: Determine willingness to make a quit attempt Ask every tobacco user if he or she is willing to make a quit attempt at this time (e.g. within the next 30 days) 4. ASSIST: Aid the patient in quitting Help the patient with a quit plan; provide practical counseling; provide intra-treatment social support; help the patient obtain extratreatment social support; recommend use of approved pharmacotherapy except in special circumstances; provide supplementary materials. 5. ARRANGE: Schedule follow-up contact Schedule follow-up contact, either in person or via telephone. 38